POS0713 BIIB059 EFFICACY IN PARTICIPANTS WITH ACTIVE CUTANEOUS LUPUS ERYTHEMATOSUS (CLE): SUBGROUP ANALYSIS OF PARTICIPANTS ACHIEVING CLEAR/ALMOST CLEAR DISEASE ACTIVITY FROM PART B OF THE TWO-PART PHASE 2 LILAC STUDY
Authors: V. Werth, R. Furie, F. Nyberg, X. Huang, C. Barbey, C. Musselli, N. Franchimont
Journal: Annals of the Rheumatic Diseases (2022)

Background CLE is an autoimmune disease that occurs with or without systemic manifestations. The chronic manifestations of CLE often have a lasting negative impact on a patient’s quality of life. 1,2 Clearance of skin activity is the most desirable outcome for a targeted treatment in patients with CLE; however, it is a challenging target to achieve. Activation of both the innate and adaptive immune systems leads to the typical inflammatory histopathological characteristics of CLE and its clinical manifestations. 3 BIIB059 is a humanized monoclonal antibody that engages blood dendritic cell antigen 2 (BDCA2), a receptor on plasmacytoid dendritic cells, inhibiting production of Type I interferons and other chemokines/cytokines. 4 The randomized Phase 2 LILAC study ( NCT02847598 ) met its primary endpoint in CLE (Part B), demonstrating a dose response in the percent change in Cutaneous Lupus Erythematosus Disease Area and Severity Index – Activity (CLASI-A) from baseline (BL) to Week 16 for BIIB059 vs placebo (PBO). 5 Objectives To determine the proportions of participants achieving a clear or almost clear skin status as defined by the attainment of CLASI-A scores of 0–1 or 0–3 at Week 16. Methods In Part B, adults with histologically confirmed active CLE with or without systemic manifestations and adjudicated BL CLASI-A ≥8 received BIIB059 (50, 150, or 450 mg) or PBO subcutaneously Q4W through Week 12, with an additional loading dose at Week 2. CLASI-A was assessed at each dosing visit and at Week 16. The proportions of participants achieving CLASI-A scores of 0–1 (prespecified analysis) or 0–3 (ad-hoc analysis) and mean absolute CLASI-A score changes at Week 16 were determined. Results At BL, mean (standard deviation [SD]) CLASI-A scores were 16.6 (8.8) and 16.5 (8.5) for the pooled BIIB059 and PBO groups, respectively. At Week 16, more participants in the BIIB059 50, 150, and 450 mg treatment groups achieved CLASI-A scores of 0–1 and 0–3 vs those in the PBO group (Table 1). In participants achieving CLASI-A scores of 0–1, mean (SD) absolute CLASI-A scores decreased by 11.0 (SD not applicable), 19.6 (11.1), and 16.4 (11.5) points from BL at Week 16 in the 50, 150, and 450 mg treatment groups, respectively; in participants achieving CLASI-A scores of 0–3, CLASI-A scores decreased by 8.8 (2.7), 15.4 (10.3), and 13.2 (9.5) points from BL at Week 16 in the 50, 150, and 450 mg treatment groups, respectively, vs 8.3 (2.5) points in the PBO group. Among the 11 participants who achieved CLASI-A scores of 0–1, six had CLASI-A scores of 0 (representing a 100% resolution of skin disease) with a decrease in CLASI-A score ranging from 11 to 30 points. Table 1. Proportion of pts who achieved CLASI-A scores of 0–1 and 0–3 BIIB059 PBO 50 mg 150 mg 450 mg (n=33) (n=26) (n=25) (n=48) Number of pts achieving CLASI-A score of 0–1 at Week 16 (%) 0/32 1/26 5/25 5/43 (0) (3.9) (20.0) (11.6) Number of pts achieving CLASI-A score of 0–3 at Week 16 (%) 3/32 5/26 8/25 9/43 (9.4) (19.2) (32.0) (20.9) Pts considered as treatment failures or who discontinued treatment were classified as non-responders at visits post treatment failure or treatment discontinuation. Pts who completed treatment but had a missing score at any primary timepoint are classified as non-responders for that timepoint. Conclusion After 16 weeks of treatment, greater proportions of participants with active CLE treated with BIIB059 vs PBO achieved a clear or almost clear skin status, defined as CLASI-A score of 0–1 or 0–3, further supporting the efficacy of BIIB059 in CLE. References [1]Ogunsanya ME, et al. Lupus 2020;29:1691–1703 [2]Ogunsanya ME, et al. Int J Womens Dermatol 2018;4:152–158 [3]Wenzel J. Nat Rev Rheumatol 2019;15:519–532 [4]Pellerin A, et al. EMBO Mol Med 2015;7:464–476 [5]Werth V, et al. Arthritis Rheumatol 2020;72(Suppl. 10):0986 (Abstract) pts, participants Acknowledgements The authors thank the LILAC investigators for their valuable contributions to the study. This study was sponsored by Biogen (Cambridge, MA, USA). Writing and editorial support was provided by Selene Medical Communications (Macclesfield, UK), funded by Biogen. Disclosure of Interests Victoria Werth Consultant of: Biogen, Grant/research support from: Biogen, Richard Furie Consultant of: AstraZeneca, Biogen, Grant/research support from: AstraZeneca, Biogen, Filippa Nyberg Consultant of: AstraZeneca, Biogen, XIAOBI HUANG Shareholder of: Biogen, Employee of: Biogen, Catherine Barbey Shareholder of: Biogen, Employee of: Biogen, Cristina Musselli Shareholder of: Biogen, Employee of: Biogen, NATHALIE FRANCHIMONT Shareholder of: Biogen, OMass Therapeutics, Consultant of: OMass Therapeutics, Employee of: Biogen